The Baltimore Longitudinal Study of Aging (BLSA) prostate aging and disease study has both retrospective and prospective arms involving repeated assessments of anatomical, physiological, hormonal, and behavioral aspects of age-associated changes in prostate size. The retrospective arm of the study examines the sex steroid and PSA levels from frozen sera stored during the three most recent visits and visits closest to 10, 15, 20 and 25 years before study initiation for active and inactive participants over the age of 40. The prospective arm involves male BLSA participants over the age of 30 and will continue for at least 10 years. Our previous work suggests that prostate cancer develops over a period of at least 10 years in most men, and that PSA can stratify men at risk as long as 20 to 30 years prior to diagnosis. During the regularly scheduled BLSA visits, the eligible participants will: 1) complete an objective symptom score analysis quantifying obstructive and irritative voiding symptoms; 2) undergo digital rectal prostatic examinations (DRE) and prostate massage by an urologist; 3) have blood drawn for assays of PSA and other prostate markers and proteomics; 4) undergo uroflow examination and sonographic determination of residual urine volume; and 5) undergo pelvic MRI. Males over age 40 who have given permission for autopsy will have the prostate gland examined pathologically after death. Over the past year, we have explored the role of dietary factors in BLSA men. Three studies have been reported. 1) Animal studies suggest that energy restriction reduces the growth of tumors, including prostate tumors. However, results from epidemiological studies of energy intake and prostate cancer risk have not been consistent. To examine the association of total energy intake and macronutrient contributors to energy with prostate cancer risk, we studied 444 men who completed at least one food frequency questionnaire (FFQ). At their earliest FFQ completion, men were aged 45-92 years old. Total prostate cancer cases (n=68) consisted of men who were diagnosed with cancer before their FFQ completion (n=46) and men who were diagnosed with cancer after their FFQ completion (n=22). Total energy intake was positively associated with prostate cancer. Compared to the lowest quintile of energy intake, the OR for the highest quintile was 3.79 (95% CI: 1.52-9.48, p-trend 0.002). Energy-adjusted intake of protein, fat, and carbohydrate were not statistically significantly associated with prostate cancer risk. This study suggests a higher risk of prostate cancer with increased energy intake. 2) Vitamin C (ascorbic acid) is a water-soluble antioxidant that is hypothesized to prevent carcinogenesis by scavenging free radicals and protecting DNA from oxidative damage. In vitro studies have demonstrated that vitamin C inhibits the growth of both androgen-independent and androgen-dependent prostate cancer cells. Although several cohort studies have examined the association between dietary intake of vitamin C and prostate cancer risk , only one study has investigated the association for plasma vitamin C. In this study, we hypothesized that high prediagnostic plasma vitamin C concentrations would be associated with a reduced risk of prostate cancer in men. Plasma vitamin C (ascorbic acid) concentrations were measured previously in blood samples drawn between 1987 and 1990. Plasma vitamin C concentrations were studied from 489 men with 57 subsequently diagnosed with prostate cancer an average 4.8 years after the blood draw (range 0.1 to 12.5 years). No inverse association was found between serum vitamin C and prostate cancer for the entire sample. Stratifying by the median age at blood draw, there was an increased risk of prostate cancer for men < 70 years old with high plasma vitamin C levels (? vs. < median, OR = 2.51, 95% CI: 1.13-5.60) but not for men ? 70 years old (? vs. < median, OR = 0.88, 95% CI: 0.36-2.13). We concluded that plasma vitamin C concentrations within the normal range are not protective against prostate cancer in adult men, though there may be an age related difference in risk associated with vitamin C. 3) We examined the association between prostate cancer and calcium and other nutrients thought to influence the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D]. The analyses included 457 men who were 46 to 92 years old at the time of completion of a food frequency questionnaire (FFQ). Among them, 69 men were diagnosed with prostate cancer during their lifetime. In 68% of the cases, the FFQ was completed before the diagnosis of cancer. Multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of prostate cancer. The adjusted OR of prostate cancer for the highest tertile compared to the lowest tertile of calcium intake was 0.92 (95% CI, 0.48-1.77; Ptrend, 0.89). Likewise, there were no significant trends for phosphorus, vitamin D, fructose, and animal protein intakes. Dairy products, including milk, were not associated with an increased risk of prostate cancer. The adjusted OR of prostate cancer was 1.26 (95% CI, 0.57-2.79; Ptrend, 0.73) for men with high dairy intakes compared to low dairy intakes. This study suggests that calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. We are currently continuing to examine the role of dietary factors on prostate disease. We are completing work on examining the risk of prostate cancer in relationship to serum testosterone levels. In addition, we are starting to evaluate the relationship of urinary symptoms to prostate diagnoses. This includes examining how changing urinary symptom scores impact on quality of life, and the time course of change in urinary symptoms.